The role of dietary polyphenols in alternating DNA methylation in cancer.

Natural products such as curcumin, quercetin, and resveratrol have been shown to have antitumor effectsand several studies have examined their role in treating cancer, either alone or in combination with other chemotherapeutic drugs. These compounds are capable of affecting different cancer-related mechanisms, such as proliferation, inflammation, invasion, and metastasis. Along with all of the benefits of these agents, affecting epigenetic processes is one of the most important aspects of their impact. Epigenetic modifications can be categorized into three main processes that include DNA methylation, histone modification, and regulation of small non-coding RNAs. Therefore, targeting DNA methylation can be used as a cancer treatment strategy by identifying or developing methylation modulators. Herein, we take a look into the studies investigating the role of natural products (e.g. curcumin, resveratrol, epigallocatechin gallate (EGCG), and quercetin) in alternating the DNA methylation status of various cancer cells. We discuss how these compounds reduce the expression of enzymes mediating the methylation of tumor suppressor genes and thereby, increasing the expression of tumor suppressors while reactivating antitumor signaling pathways.

In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide.

Morinda elliptica L. (Rubiaceae) is a phytomedicinal herb, used to treat gastrointestinal complications in Peninsular Malaysia. The study evaluates the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats. Thirty adult rats were divided into five groups of six rats each. Rats of the normal control group received intraperitoneal injections (i. p.) of vehicle 10% Tween-20, 5 ml/kg, and hepatotoxic group 200 mg/kg TAA three times per week respectively. Three supplementary groups were treated with TAA plus daily oral silymarin (50 mg/kg) or M. elliptica (250 or 500 mg/kg). After 8 weeks of treatment, all rats were sacrificed. Liver fibrosis was assessed by gross macroscopic and microscopic tissue analysis, histopathological, and biochemical analysis. The livers of the TAA treated group showed uniform coarse granules, hepatocytic necrosis with lymphocytes infiltration. Contrary, the livers of M. elliptica treated groups (250 and 500 mg/kg) were much smoother and the cell damage was much lesser. The livers of M. elliptica treated groups rats showed elevated activity of SOD and CAT with a significant decrease in MDA level at p < .0001. The level of liver damage parameters, that is, ALP, ALT, and AST, bilirubin, total protein, and albumin were restored to the normal comparable to silymarin. M. elliptica stem extract significantly promoted normal rat liver architecture with significant perfections in biochemical parameters. The molecular contents of M. elliptica with hepatoprotective influence could be discovered, is the future prospective of this study.

Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity.

AIM: Among therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation. METHODS: In this paper, the inhibitory effect of cerium oxide (CeO2) NPs against α-synuclein (α-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of α-syn amyloid either alone or with CeO2 NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays. RESULTS: ThT and ANS fluorescence assays indicated that CeO2 NPs inhibit the formation of aggregated species and hydrophobic patches of α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and ß-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of α-syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of α-syn is disaggregated in the presence of CeO2 NPs. Moreover, cellular assays depicted that CeO2 NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with α-syn amyloids. CONCLUSION: It may be concluded that CeO2 NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.